Culturing knowledge in stem cell research

2-16-16 Science Round Up, Sponsored by Biotechne

We are on a short break from our audio podcast; however, we are still delivering our science round ups in written form here on our stem cell blog.

This Science Round Up is brought to you by Biotechne. Bio-Techne brings together the prestigious life science research brands of R&D Systems, Novus Biologicals, Tocris Bioscience, and Protein Simple to provide stem cell researchers with high quality reagents that will optimize and standardize their workflow.

This Science Round Up includes several research paper and article summaries including papers covering: the Zika Virus, making mice live longer, insight into concussions, putting stem cells to sleep and waking them up later, FDA cracking down on stem cell clinics, stem cells responsible for baldness, making neurons that regulate our gut, ghost fibers, and a review on making motor neurons for spinal injury. Enjoy.

By now, I am sure all of you have heard and been following the Zika virus story. There are tons of articles out there for you read, but this link provides a good summary and and update. The Zika virus outbreak seems to have emerged out of South America, where mosquitos can carry the virus from an infected person and then spread it to others through biting. While the virus tends to have mild effects on the general population (in fact, most people don’t even know they are infected), it’s the infection of pregnant woman that seems to be the problem. It seems that if pregnant women are infected with the Zika virus, the developing fetus can become infected and lead to a symptom known as microcephaly, or babies born with small heads. Recently, it was found that the Zika virus can be spread through sex, not just by mosquitos. This led the CDC to come out with new guidelines suggesting that if you are pregnant and and your partner has traveled to parts of the world/country infected with Zika, to use condoms when engaging in sexual activity to prevent Zika spread. As expected, the virus has now spread throughout the U.S., with over fifty infections now reported. Nearly all cases were contracted outside the U.S., with Texas and Florida having the highest numbers of infection. To combat this surge of Zika infection, President Obama has asked Congress for $1.8 billion to help combat this virus on all fronts. Let’s see how Congress responds–as we all know, Congress tends to not do much of anything nowadays.

As we get older, we get more tired and “worn out”. Our bedtime gets earlier, it takes us longer to get up, and those Saturday nights of drinking with buddies just don’t end the same way they used to like when we were younger. At the cellular level, as we age, cells begin to slow down and enter a process known as senescence, where they can no longer divide/grow even in the presence of growth signals. The reason this is believed to occur is because as cells age they accumulate DNA mutations and mutated DNA can turn cells into cancer. By entering senescence, this eliminates their ability to continue dividing and becoming tumorigenic. In a new study published in Nature, researchers found that if they removed these senescent cells, the lifespan of older mice was significantly increased as much as 27%. In addition, removing these cells also increased liver, kidney and heart function. The way they did this was pretty cool. In senescent cells, a protein called p16 builds up and this buildup is a trigger for senescence. Using molecular biology, the researchers hooked up a gene that induces cells to commit suicide to a piece of DNA involved in making p16. The result is when p16 was made, so would the suicide gene and that would result in the cell dying– allowing for the removal of these senescent cells. A very cool approach. This offers a more targeted approach to aging, by specifically killing “old cells” in a certain region of the body.

The topic of concussion and brain injury has been very popular in our country over the past few years, particularly because of the historic rise of CTE cases and brain damage occurring in football players. This is obviously very scary and as parents of children who play sports where kids’ heads are banging around, even in “non-contact” sports there is significant concern. In fact, the U.S. banned the use of “headers” (hitting the ball with your head) in soccer for kids ages eleven and under. A concussion is a traumatic brain injury that alters the way our brain functions and usually results in a temporary loss of brain function. The effects are usually temporary but can include headaches and problems with concentration, memory, balance and coordination. Although concussions are typically caused by a blow to the head, they can also occur when the head and upper body are violently shaken. These injuries can cause a loss of consciousness, but most concussions do not. In a recent study published in the American Journal of Pathology, researchers suggest that while the brain can recover from one single hit to the head, successive blows to the head are where the real damage can occur. Using mice as a model, the researchers showed that if mice had time to rest and recover from their first head trauma before another, the damage was significantly less than when these head traumas were successive.

Ahh yes, I saw this headline and I had to read the paper. I’m sure all of you out there have had a bad bout of gas, bloating, etc. For some people, this is not a passing thing–no pun intended– but could be a chronic problem that might indicate some more serious ailment. Currently there are ways doctors can infer the levels of gas trapped inside us; however, they are not really the most accurate techniques. Researchers in Australia have created a 3.5 centimeter capsule that contains sensors. Once ingested, it reports the levels of different gases in the digestive track to a smartphone. This capsule has been used so far in pigs and the results are reported in the Journal of Gastroenterology. Sounds very cool; go take a look at this capsule. It doesn’t look like it’s something supposed to be digested, which means it goes in and then it comes out 🙂

I learned something new reading this article, so I had to write it up. There is a biological process called diapause that I was previously unaware of. Diapause is the delay in development in response to regularly and recurring periods of adverse environmental conditions. It’s considered to be a physiological state of dormancy with very specific initiating and inhibiting conditions, almost like a suspended animation. It is as though diapause is a mechanism used as a means to survive unfavorable environmental conditions, such as temperature extremes, drought, or reduced food availability. Diapause is most often observed in insects and in the embryos of many of the species of fish. The cool part about diapause is that once it is induced in an organism, only certain other stimuli are capable of bringing the organism out of diapause. Ok, now that we had that science lesson, let’s talk about this new paper. As many reading this already know, pluripotent stem cells possess the unique ability to differentiate or turn into all cell types of the body. In terms of regenerative medicine, scientists try to harness this ability by keeping these stem cells pluripotent in a culture dish until they are ready to differentiate them into the cell type of interest. Now, keeping a cell in the pluripotent state can be difficult, and there is a whole business out there selling products to do so. In a new paper published in ACS Central Science, scientists thought they might be able to completely stop pluripotent stem cells altogether by mimicking diapause. How were they going to do it? Well, they knew that embryos in diapause are normally covered in a thick type of mucus, so they reasoned they could engineer some sort of gel that they can embed the stem cells into mimicking this. Using hydrogel, a soft polymer used often in tissue engineering, they embedded the stem cells in this matrix and successfully stopped their differentiation potential. When they liquified the hydrogel, the stem cells essentially “woke up”, started dividing, and allowed them to carry on as good little stem cells.

We have talked about this a lot on the podcast and I am happy to see that the Food and Drug Administration (FDA) is now stepping up to regulate stem cell therapies. There are now over two hundred clinics around the U.S. that claim to have stem cell therapies fix a wide variety of ailments. Because the “stem” cells are harvested from the patients’ own bodies, these doctors and clinics have been able to sidestep a lot of regulation; however, it by no suggests these procedures are safe and effective. Enter the FDA. Recently the FDA issued rough guidelines stating that adult stem cells used in most clinics are similar to drugs and as such. must undergo a strict approval process before patients can use them. Additionally, it was reported that the FDA sent a warning letter to stem cell clinics in certain states about their unlicensed use. In as statement released last year by the FDA, they were concerned (as are many) that the strong hope patients have for cures that are not yet available may leave them vulnerable to unverified providers of stem cell treatments that are illegal and potentially harmful. The link to the FDA guidelines can be found here.

Ok everyone, say it with me: what’s our favorite journal? PPPPPPPPPP-NAS!! Thats right ,the Proceedings of the National Academy of Sciences published a paper by a group of researchers from San Diego reporting the printing of liver cells derived from stem cells. Pluripotent stem cells are used to generate all cell types of the body and has been reported previously that liver cells can be produced from stem cells. In fact, it has been reported that rudimentary liver buds, or what we call organoids, can be made from stem cells. But until now, no one has reported the bio-printing of liver cells derived from stem cells. This is pretty cool and the pictures are great. I urge you to check this out. They printed these cells in a hexagonal-like pattern, a shape that more resembles the in vivo structure of these cells. In addition to printing the cells, they also arranged them with fat cells and blood vessels to more recapitulate a functioning tissue. Cell printing is so cool.

The enteric nervous system, or ENS, is a complex network of neurons and support cells that governs the gastrointestinal system of our bodies. The ENS is quite interesting; although it receives considerable innervation from the autonomic nervous system, it can and does operate independently of the brain and the spinal cord. Because it can act on its own, the ENS has been described as the second brain. In a way, the gut has a mind of its own…(see what I did there?) Obviously, the ENS is crucial for the normal function of our GI system but there are diseases, some genetic, that specifically affect the ENS. One such disease is Hirschsprung Disease (HSCR), which is caused by the developmental failure of ENS progenitor cells to migrate into the GI tract, particularly the distal colon. To better understand this developmental failure, we would need to have a good model of human ENS development and to date this has not been achieved. Until now, thank you, stem cells. A new paper published in Nature out of Lorenz Studer’s lab demonstrates the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. Even more cool, these ENS precursors derived in the culture dish are capable of migration in the developing chick embryo and extensive colonization of the adult mouse colon. To take it to the next level, the engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related death in mice with HSCR. This study establishes the first,human PS-cell-based platform for the study of human ENS development, and presents cell and drug-based strategies for the treatment of HSCR. Very cool.

When we are young with a beautiful head of hair, we don’t think that one day those gorgeous locks might disappear, leaving us with not much cover on top. But losing hair as we age is a sad reality. Baldness, or hair loss, is a consequence of age. But why? In a new paper published in Science, Japanese researchers provide us with a potential answer and look to stem cells as the culprit. Like most cells in our body that renew, hair is constantly produced from stem cells that sit deep within the hair follicle. This is well and good, but eventually, as we age, these stem cells start to age and subsequently lose the ability to make new hair. This group of researchers found that over time, the DNA of these cells gets damaged and this causes chemical changes that push the hair follicle away from growing new hair, making it more difficult for a new hair to grow. So basically, our hair follicles disintegrate over time and wither away. What accelerates this process are things that cause DNA damage. like UV from sunlight and chemicals that we put in our hair every day. So everyone–be kind to your hair stem cells or they will not be kind to you– leaving you with a great big bald spot on top.

Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis are two devastating diseases that affect the spinal cord with little to no therapeutic options. Stem cells have been touted as a potential new therapeutic option by being able to generate the motor neurons that degenerate in these diseases for possible replacement therapies and discovery of new drugs. In a new review published out of the University of London, the author reviews the current landscape of the development of motor neurons, and the latest information on stem cell derived motor neurons for potential therapies.

I had to include this because it has the term “ghost fibers” in it: how stem cells and their immediate progenitors rebuild tissues. In a new paper published in Cell Stem Cell, researchers used 3-D, time-lapse intravital imaging for direct visualization of the muscle regeneration process in live mice. The authors show that the extracellular matrix remnants from injured skeletal muscle fibers, which they call “ghost fibers,” govern muscle stem/progenitor cell behaviors during regeneration. They found that the stem cells were immobile and quiescent without injury, whereas their activated progenitors migrated and divided after injury. What they found unexpectedly was that divisions and migration were primarily bidirectionally oriented along the ghost fiber longitudinal axis, allowing for spreading of progenitors throughout ghost fibers. The authors conclude that ghost fibers are autonomous, architectural units necessary for proportional regeneration after tissue injury. This finding reinforces the need to fabricate bio-engineered matrices that mimic living tissue matrices for tissue regeneration therapy.

We hope you enjoyed this Science Round Up, brought to you by Biotechne. Please leave comments or questions you might have below.